ID   EASG_EPIFI              Reviewed;         309 AA.
AC   A2TBU1;
DT   15-MAR-2017, integrated into UniProtKB/Swiss-Prot.
DT   06-MAR-2007, sequence version 1.
DT   25-MAY-2022, entry version 47.
DE   RecName: Full=Agroclavine dehydrogenase {ECO:0000250|UniProtKB:P0CT21};
DE            EC=1.5.1.46 {ECO:0000250|UniProtKB:P0CT21};
DE   AltName: Full=Ergot alkaloid biosynthesis protein G {ECO:0000303|PubMed:17308187};
GN   Name=easG {ECO:0000303|PubMed:17308187};
OS   Epichloe festucae var. lolii (Neotyphodium lolii) (Acremonium lolii).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC   Hypocreomycetidae; Hypocreales; Clavicipitaceae; Epichloe.
OX   NCBI_TaxID=73839;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND INDUCTION.
RC   STRAIN=Lp19;
RX   PubMed=17308187; DOI=10.1128/aem.00257-07;
RA   Fleetwood D.J., Scott B., Lane G.A., Tanaka A., Johnson R.D.;
RT   "A complex ergovaline gene cluster in epichloe endophytes of grasses.";
RL   Appl. Environ. Microbiol. 73:2571-2579(2007).
RN   [2]
RP   FUNCTION.
RX   PubMed=11592979; DOI=10.1073/pnas.221198698;
RA   Panaccione D.G., Johnson R.D., Wang J., Young C.A., Damrongkool P.,
RA   Scott B., Schardl C.L.;
RT   "Elimination of ergovaline from a grass-Neotyphodium endophyte symbiosis by
RT   genetic modification of the endophyte.";
RL   Proc. Natl. Acad. Sci. U.S.A. 98:12820-12825(2001).
CC   -!- FUNCTION: Agroclavine dehydrogenase; part of the gene cluster that
CC       mediates the biosynthesis of fungal ergot alkaloid ergovaline, the
CC       predominant ergopeptine product in E.festucae var. lolii
CC       (PubMed:17308187). DmaW catalyzes the first step of ergot alkaloid
CC       biosynthesis by condensing dimethylallyl diphosphate (DMAP) and
CC       tryptophan to form 4-dimethylallyl-L-tryptophan (By similarity). The
CC       second step is catalyzed by the methyltransferase easF that methylates
CC       4-dimethylallyl-L-tryptophan in the presence of S-adenosyl-L-
CC       methionine, resulting in the formation of 4-dimethylallyl-L-abrine (By
CC       similarity). The catalase easC and the FAD-dependent oxidoreductase
CC       easE then transform 4-dimethylallyl-L-abrine to chanoclavine-I which is
CC       further oxidized by easD in the presence of NAD(+), resulting in the
CC       formation of chanoclavine-I aldehyde (By similarity). Agroclavine
CC       dehydrogenase easG then mediates the conversion of chanoclavine-I
CC       aldehyde to agroclavine via a non-enzymatic adduct reaction: the
CC       substrate is an iminium intermediate that is formed spontaneously from
CC       chanoclavine-I aldehyde in the presence of glutathione (By similarity).
CC       The presence of easA is not required to complete this reaction (By
CC       similarity). Further conversion of agroclavine to paspalic acid is a
CC       two-step process involving oxidation of agroclavine to elymoclavine and
CC       of elymoclavine to paspalic acid, the second step being performed by
CC       the elymoclavine oxidase cloA (By similarity). Paspalic acid is then
CC       further converted to D-lysergic acid (By similarity). Ergovaline is
CC       assembled from D-lysergic acid and three different amino acids by the
CC       D-lysergyl-peptide-synthetase composed of a monomudular (lpsB) and a
CC       trimodular (lpsA) nonribosomal peptide synthetase subunit
CC       (PubMed:17308187, PubMed:11592979). {ECO:0000250|UniProtKB:P0CT21,
CC       ECO:0000269|PubMed:11592979, ECO:0000269|PubMed:17308187}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=agroclavine + NADP(+) = didehydroagroclavine + H(+) + NADPH;
CC         Xref=Rhea:RHEA:34059, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783,
CC         ChEBI:CHEBI:58349, ChEBI:CHEBI:65036, ChEBI:CHEBI:65042; EC=1.5.1.46;
CC         Evidence={ECO:0000250|UniProtKB:P0CT21};
CC   -!- PATHWAY: Alkaloid biosynthesis; ergot alkaloid biosynthesis.
CC       {ECO:0000305|PubMed:17308187}.
CC   -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:P0CT21}.
CC   -!- INDUCTION: Strongly expressed in planta but weakly expressed in axenic
CC       culture (PubMed:17308187). {ECO:0000269|PubMed:17308187}.
CC   -!- SIMILARITY: Belongs to the fgaFS/easG family. {ECO:0000305}.
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DR   EMBL; EF125025; ABM91452.1; -; Genomic_DNA.
DR   AlphaFoldDB; A2TBU1; -.
DR   SMR; A2TBU1; -.
DR   UniPathway; UPA00327; -.
DR   GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR   GO; GO:0035835; P:indole alkaloid biosynthetic process; IEA:UniProtKB-UniPathway.
DR   InterPro; IPR019901; Ergot_alkaloid_biosynthesis.
DR   InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR   InterPro; IPR008030; NmrA-like.
DR   Pfam; PF05368; NmrA; 1.
DR   SUPFAM; SSF51735; SSF51735; 1.
DR   TIGRFAMs; TIGR03649; ergot_EASG; 1.
PE   2: Evidence at transcript level;
KW   Alkaloid metabolism; NADP; Oxidoreductase.
FT   CHAIN           1..309
FT                   /note="Agroclavine dehydrogenase"
FT                   /id="PRO_0000439144"
SQ   SEQUENCE   309 AA;  34267 MW;  41909BE716D55815 CRC64;
     MVQIYLPRLS MRLGYHDKNN KMTILLTGGR GKTASHIASL LQAAKVPFIV ASRSSDPSSS
     SPYYQNCFDW LDEKTYGDVL TSKDSMQPIS TIWLVPPPIF DLAPLMIKFV DFASRKGVKR
     FVLLSASTIK KGGPAMGQVH EYLASLGGIE YAVLRPTWFM ENFSYPQELQ RLAIKNENKI
     YSAAGDGKLP FVSVADIARV AFRTLTDEKS HNTDYVLLGP ELITYDQVAE TLSTVLGRTI
     THIKLTEEEL VKRLENSGMP AEDAKMLAGM DTSISDGAED RLNNVVKHVT GADPRTFLDF
     ATHQKATWG